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Culturing and Measuring Fetal and Newborn Murine Long Bones
Published on: April 26, 2019
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A maternal brain hormone that builds bone
Muriel E Babey1, William C Krause2, Kun Chen3
1Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Francisco, San Francisco, CA, USA.
Nature
|July 10, 2024
Summary
Cellular Communication Network factor 3 (CCN3) from brain neurons builds bone in lactating mothers. This hormone supports bone mass and ensures offspring survival, offering potential new therapies for bone loss.
Area of Science:
- Neuroendocrinology
- Skeletal Biology
- Reproductive Biology
Background:
- Lactation causes significant bone loss in mothers due to high calcium demands.
- Estrogen levels drop postpartum, reducing bone protection.
- A previously observed female-specific dense bone phenotype suggested a humoral factor involved.
Purpose of the Study:
- To identify the humoral factor responsible for bone mass regulation during lactation.
- To investigate the role of brain-derived Cellular Communication Network factor 3 (CCN3) in bone metabolism.
- To determine if CCN3 acts as an osteoanabolic hormone.
Main Methods:
- Identification of CCN3 as the humoral factor secreted by arcuate nucleus KISS1 (ARCKISS1) neurons.
- Assessing CCN3's effect on mouse and human skeletal stem cell activity in vitro.
- Evaluating CCN3's impact on bone remodeling and fracture repair in mice.
- Manipulating CCN3 expression in ARCKISS1 neurons of lactating mice.
Main Results:
- CCN3 stimulates skeletal stem cell activity and osteochondrogenic potential.
- CCN3 promotes bone remodeling and accelerates fracture repair in both young and old mice.
- Reduced CCN3 levels in lactating mothers led to bone loss and impaired offspring survival on a low-calcium diet.
- CCN3 expression in ARCKISS1 neurons increases during lactation.
Conclusions:
- CCN3 is a novel, brain-derived osteoanabolic hormone crucial for maintaining bone mass during lactation.
- CCN3 acts as a maternal hormone essential for offspring survival.
- CCN3 represents a potential therapeutic target for treating bone loss in both sexes.
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